Rheumatoid arthritis (RA) is an autoimmune, inflammatory condition that affects peripheral joints. Collagen-induced arthritis animal models have helped define genes related to RA conditions. A major histocompatibility complex (MHC) class II gene (Aq in mouse) important for the initiation and maintenance of RA conditions has been identified. This gene functionally corresponds to the HLA-DR gene DR*0401 in humans, suggesting that T cell mediated autoimmune recognition of joint specific antigens is involved in the disease.
Genes in regions outside the MHC also have been found to be important for the initiation and maintenance of RA conditions. One of these gene regions is located on chromosome 2 in mouse and contains a gene coding for the complement factor C5. One of the active components of C5 is C5a, which is released during complement binding to immunocomplexes. The release of C5a triggers several different pathways that lead to rheumatoid inflammation. C5a produced locally in an inflammatory joint can bind to receptors on macrophages and neutrophilic granulocytes, leading to infiltration of inflammatory cells into joints. C5 also plays a central role in complement-mediated processes such as sepsis, myocardial ischemia/reperfusion injury, adult respiratory distress syndrome, nephritis, and graft rejection, as well as complement-mediated inflammatory conditions such as rheumatoid arthritis, asthma, inflammatory bowel disease, multiple sclerosis, arteriosclerosis, and vasculitis.